GRACE
CHANG, M. D. , M. P. H. , is an associate professor of psychiatry at
Harvard Medical School, Department of Psychiatry, Brigham and Women
s Hospital, Boston, Massachusetts.
Preparation of this article was supported in part by National Institute
on Alcohol Abuse and Alcoholism grants K24 AA 00289 and R01 AA 12548.

According
to new studies, even low levels of prenatal alcohol exposure can negatively
affect the developing fetus, thereby increasing the importance of identifying
women who drink during pregnancy. In response, researchers have developed several
simple alcohol-screening instruments for use with pregnant women. These instruments,
which can be administered quickly and easily, have been evaluated and found
to be effective. Because of the potential adverse consequences of prenatal alcohol
exposure, short screening questionnaires are worthwhile preventive measures
when combined with appropriate followup. KEY
WORDS: prenatal alcohol exposure; prenatal diagnosis; alcohol use test; identification
and screening for AOD (alcohol or other drug) use; specificity and sensitivity
of measurement; breath alcohol analysis; AODR ( alcohol-or other drug-related)
biological markers

Screening pregnant women
for alcohol use has become of increasing importance, because new research
indicates that even low levels of prenatal alcohol exposure can negatively
affect the developing fetus. Adverse effects of prenatal alcohol exposure
can range from subtle developmental problems, or fetal alcohol effects, to
full-blown fetal alcohol syndrome. In addition, scientists and clinicians
have found that certain neurobehavioral outcomes associated with prenatal
alcohol exposure can persist in the affected person into adolescence (Sampson
et al. 1994) and adulthood (Kelly et al. 2000) .

Because no universally safe level of alcohol consumption during pregnancy
has been identified (Stratton et al. 1996), the U. S. Surgeon General and
the Secretary of Health and Human Services recommend abstinence both before
conception and throughout pregnancy ( Stratton et al. 1996; Ebrahim et al.
1998) . However, approximately 20 percent of women drink some alcohol during
pregnancy, and the rate of frequent drinking ( i. e. , seven or more drinks
per week or five or more drinks per occasion) by pregnant women has increased
substantially, from 0.8 percent in 1991 to 3.5 percent in 1995 ( Ebrahim et
al. 1998; Centers for Disease Control and Prevention 1997) . This rise in
the rate of alcohol consumption among pregnant women coincides with growing
evidence of the negative effects of low-to-moderate alcohol consumption during
pregnancy.

Increasingly sophisticated research has improved scientific and clinical understanding
of the adverse consequences of prenatal alcohol exposure. The term pregnancy
risk drinking ( i. e. , drinking during pregnancy at levels considered risky
to the fetus) was previously defined as the consumption of 1 ounce or more
of alcohol ( i. e. , two or more drinks) per day ( Sokol et al. 1989) , but
more recent findings show that even lower levels of alcohol consumption can
lead to negative pregnancy outcomes ( Charness et al. 1994; Wong et al. 1995;
Ikonomidou et al. 2000; Jacobson and Jacobson 1994) . A study of more than
5,000 pregnant women who consumed alcohol moderately ( defined as at least
3.5 drinks per week) demonstrated that the women who drank more than 3.0 drinks
per week increased significantly their risk of first-trimester spontaneous
abortion ( Windham et al. 1997) .

Identifying women who
drink at risky levels during pregnancy poses special challenges, however,
particularly because the definition of pregnancy risk drinking has been refined
over time. In addition, screening for any alcohol use during pregnancy
is difficult. This article discusses the difficulties involved in screening
pregnant women for alcohol use; details some of the questionnaires, or instruments,
available to facilitate alcohol screening in this population; and briefly
describes a few laboratory tests used for detecting alcohol use among pregnant
women.

Complications of Screening
Pregnant Women for Alcohol Use

A key complication in
screening pregnant women for alcohol use arises from the fact that the traditional
alcohol-screening questionnaires - such as the Michigan Alcoholism Screening
Test (MAST) ( Selzer 1971) and the CAGE1 ( Ewing 1984) - are less
effective in identifying drinking problems among women than among men - (1The CAGE screening instrument
( Ewing 1984) consists of four questions: ( 1) Have you ever felt you should
Cut down on your drinking? , ( 2) Have people Annoyed you by criticizing your
drinking? , ( 3) Have you ever felt bad or Guilty about your drinking? , and
( 4) Have you ever had a drink first thing in the morning to steady your nerves
or to get rid of a hangover ( Eye opener) ?). This discrepancy is attributable
to the fact that these instruments were developed among men, who have different
patterns of alcohol consumption and different thresholds for problem drinking
than women ( Babor et al. 1989) . In addition, these instruments were developed
to detect alcohol dependence, which is relatively uncommon among pregnant
women ( Ebrahim et al. 1998) . Because of biological differences between women
and men, the same quantity of alcohol consumed over the same time period produces
higher blood alcohol levels in women than in men ( Graham et al. 1998) . Women
are also more sensitive than men to alcohol-related organ damage, such as
cardiomyopathy and myopathy (Urbano-Marquez et al. 1995; Hanna et al. 1992)
. Therefore, alcohol-screening-instrument cutoff scores ( i. e. , the values
that clinicians use to define a positive result from a screening instrument)
most likely need to be set differently for men and women and particularly
for pregnant women (Bradley et al. 1998) .

A second complication faced by researchers is that many women alter their
alcohol consumption once they learn that they are pregnant. Consequently,
inquiries about drinking patterns before pregnancy confirmation are potentially
more accurate measures of first-trimester drinking (Day et al. 1993) . Women
are also likely to deny or minimize their drinking during pregnancy out of
embarrassment (Morrow-Tlucak et al. 1989) . Even moderate drinkers may underreport
alcohol consumption during pregnancy (Verkerk 1992) . Data from a sample of
361 mothers suggest that women who report drinking more than 1.3 drinks per
week during pregnancy actually may be drinking at levels high enough to incur
risk for alcohol-related birth defects (Jacobson et al. 1991) . For example,
53 percent of the women who reported drinking more than 1.3 drinks per week
during pregnancy reported higher levels of consumption when interviewed retrospectively.

A third complication is
that standard questions about quantity and frequency of alcohol consumption
are unlikely to be helpful when screening pregnant women for alcohol use.
The widely used American College of Obstetricians and Gynecologists ( ACOG)
Antepartum Record poses three questions about alcohol use: ( 1) the amount
of alcohol consumed per day before pregnancy, ( 2) the amount of alcohol consumed
per day during pregnancy, and ( 3) the number of years of alcohol use. The
Antepartum Record has a fill-in-the-boxes format designed to gather standard
clinical information on obstetric patients. However, compared with the 13-item
Prenatal Alcohol Use Interview, the ACOG Antepartum Record is less successful
in identifying prenatal alcohol use. Researchers suggest that the difference
in findings between the two instruments may be attributable to the format
of the ACOG Antepartum Record and its lack of guiding questions: the ACOG
instrument requires a skilled interviewer in order to elicit accurate responses
about drinking during pregnancy ( Budd et al. 2000) .

A final complication is that obstetricians inconsistently screen their patients
for alcohol use during pregnancy. One goal of Healthy People 2000 was to increase
obstetricians' rate of screening for alcohol use to 75 percent, from the 1987
rate of 34 percent ( Stratton et al. 1996) . Progress toward this goal has
not yet been reported. In response to the need for increased alcohol screening
among pregnant women, researchers have developed several alcohol-screening
instruments specifically for use with this population.

Screening Instruments

The screening instruments
described in this section were tested in diverse clinical populations and
may help identify women using alcohol during pregnancy. These instruments
vary in that they were designed to detect different levels of alcohol use
and, therefore, differ in how they define pregnancy risk drinking.

In general, a positive
screen does not indicate an alcoholism diagnosis; rather, it may signal to
a physician or other health care practitioner the need to discuss pregnancy
risk drinking with a patient. Routine use of screening questionnaires in clinical
practices may reduce the stigmatization of asking patients about alcohol use
and result in more accurate and consistent evaluation.

Sensitivity and specificity
are two important properties of every screening instrument. The sensitivity
of a screening test refers to the probability that a person who should
test positive, does so ( i. e. , the sensitivity of a screen for pregnancy
risk drinking is the probability that a woman who is a risk drinker tests
positive) . The specificity of a screening test is the probability
that a person who should test negative, does so ( i. e. , the probability
that a woman who is not a risk drinker tests negative) (Rosner 1990) .

The T-ACE

The T-ACE was the
first validated sensitive screen for risk drinking (defined as alcohol consumption
of 1 ounce or more per day) developed for use in obstetric-gynecologic practices
( Sokol et al. 1989) . An obstetrician developed the T-ACE after observing
that asking patients about their tolerance to the intoxicating effects of
alcohol did not trigger denial. The "socially correct" answer is
not known (patients do not feel stigmatized to answer honestly), and tolerance
reflects a pattern of drinking.

The four T-ACE questions (see T ­ ACE textbox) take less than 1 minute to
ask. The T-ACE is positive with a score of 2 or more points. One point is
given for each affirmative answer to the A, C, or E questions. Two points
are given when a pregnant woman reports that more than two drinks are necessary
for her to feel "high" or experience the intoxicating effects of
alcohol.

Researchers initially evaluated the T-ACE in a sample of 971 African-American
women attending an inner-city antenatal clinic. The researchers administered
both the MAST and CAGE as well as asked the T-ACE tolerance question, How
many drinks does it take to make you feel high? The T-ACE was not administered
as an independent instrument; instead, both the sensitivity and specificity
of the T-ACE were calculated from the subjects responses to the tolerance
question as well as to the annoyed, cut-down, and eye-opener questions from
the CAGE questionnaire. The T-ACE proved to be superior to both the MAST and
CAGE in identifying pregnancy risk drinking ( i. e. , defined as alcohol consumption
of more than 1 ounce daily) . Table 1 summarizes the study' s findings.

MAST
= Michigan Alcoholism Screening Test.
* Pregnancy risk drinking is defined as the consumption of 1 ounce or
more of alcohol per day during pregnancy. NOTE: The sensitivity of
a screening test is the probability that a person who should test positive,
does so ( i. e. , the sensitivity of a screen for pregnancy risk drinking
is the probability that a woman who is a risk drinker tests positive)
. The specificity of a screening test is the probability that
a person who should test negative, does so ( i. e. , the probability
that a woman who is not a risk drinker tests negative) ( Rosner 1990)
.
SOURCE: Sokol et al. 1989.

T-ACE

T
Tolerance: How many drinks does it take to make you feel high?

A Have people Annoyed you by criticizing your drinking?

C Have you
ever felt you ought to Cut down on your drinking?

E Eye opener: Have you ever had a drink first thing in the morning
to steady your nerves or get rid of a hangover?

The T-ACE is used
to screen for pregnancy risk drinking, defined here as the consumption
of 1 ounce or more of alcohol per day while pregnant. Scores are calculated
as follows: a reply of More than two drinks to question T is considered
a positive response and scores 2 points, and an affirmative answer to
question A, C, or E scores 1 point, respectively. A total score of 2
or more points on the T-ACE indicates a positive outcome for pregnancy
risk drinking.

SOURCE: Sokol et al. 1989.

We subsequently tested
the T-ACE as a self-administered, independent screening tool embedded in a
health-habits survey with questions about smoking, stress, weight, and dietary
habits in a more socially and ethnically diverse obstetric population - 350
women initiating prenatal care at the Brigham and Women' s Hospital in Boston,
Massachusetts (Chang et al. 1998) .

We compared the sensitivity and specificity of the T-ACE with the sensitivity
and specificity of three other popular methods of screening for alcohol use
in other clinical settings: (1) the Alcohol Use Disorders Identification Test
( AUDIT) (Babor et al. 1992), (2) the Short Michigan Alcoholism Screening
Test ( SMAST) (Selzer et al. 1975) , and (3) a review of the patient s medical
record. Researchers gave each participant the AUDIT and SMAST independently
as well as reviewed the participant s medical record. The three criteria
used to evaluate the T-ACE, AUDIT, SMAST, and medical record were as follows:
( 1) alcohol abuse or dependence diagnoses as defined according to the Diagnostic
and Statistical Manual of Mental Disorders, Third Edition, Revised ( DSM-III-R)
(American Psychiatric Association 1987) , which the subject could meet at
any point in her lifetime; (2) risk drinking, defined as having more than
two drinks per drinking day before pregnancy; and (3) current drinking ( i.
e. , any alcohol consumption during pregnancy) .
Table 2 summarizes the sensitivity and specificity of the T-ACE, AUDIT, SMAST,
and medical record for the three criteria. In addition, sensitivity and specificity
for varying cut-off scores for the T-ACE and AUDIT are listed (e. g. , in
response to the tolerance question in the T-ACE, "more than 2 drinks"
would be a positive response in one scoring method and 2 or more drinks would
be a positive response when using a different scoring method) . With "tolerance"
defined as "2 or more drinks to feel intoxicated", the T-ACE was
the most sensitive instrument to detect current alcohol consumption, risk
drinking, and lifetime DSM-III-R alcohol diagnoses. However, it was also the
least specific.

Table 2 Sensitivity
and Specificity of the T-ACE, AUDIT, SMAST,
and Medical Record

Criterion Standard

Instrument

Sensitivity* (
% )

Specificity*
* ( % )

DSM-III-R lifetime
alcohol diagnosis

T-ACE (tolerance
>= 2)

87.8

36.6

T-ACE (tolerance
> 2)

60.0

66.4

AUDIT (>= 11)

7.0

99.6

AUDIT (>= 10)

11.0

99.0

AUDIT (>= 8)

22.6

97.4

SMAST

14.8

97.9

Medical record

15.6

93.6

Risk drinking (
two drinks per day before pregnancy)

T-ACE (tolerance
>= 2)

92.4

37.6

T-ACE (tolerance
> 2)

74.3

71.4

SMAST

11.4

95.9

Medical record

6.7

89.4

Current alcohol
consumption(while pregnant)

T-ACE (tolerance
>= 2)

89.2

37.8

T-ACE (tolerance
> 2)

60.0

66.9

AUDIT (>= 11)

3.3

97.8

AUDIT (>= 10)

6.7

96.9

AUDIT (>= 8)

15.0

93.9

SMAST

7.5

94.3

Medical record

20.0

96.1

SMAST
= Short Michigan Alcoholism Screening Test.
* Sensitivity is the probability that a person who should test positive,
does so ( Rosner 1990).
* * Specificity is the probability that a person who should test negative,
does so ( Rosner 1990) . NOTE: The sensitivity and specificity for varying
cutoff scores for the T-ACE and AUDIT are listed(e. g. , in response to the tolerance question in the T-ACE,
more than two drinks would be a positive response in one scoring method
and two or more drinks would be a positive response under a different
scoring method). With tolerance defined as two or more drinks to feel
intoxicated, the T-ACE was the most sensitive instrument to detect current
alcohol consumption, risk drinking, and lifetime DSM-III-R alcohol diagnoses.
However, it was also the least specific.
SOURCE: Chang et al. 1998.

The ideal screening test
would be both highly sensitive and highly specific; however, any given test
usually has a trade off. Screeners typically give priority to sensitivity
if it is important to identify a condition, even if more false positives are
subsequently identified. However, if insufficient resources are available
to evaluate all patients who screen positive, then specificity may be considered
more important ( Russell 1994) . Thus, the T-ACE, with a positive response
to the tolerance question defined as "more than 2 drinks", offers
the best balance of sensitivity and specificity.

The T-ACE is a valuable and efficient tool for identifying alcohol use among
pregnant women; in addition, it demonstrates acceptability and accuracy in
identifying a range of alcohol-use levels in diverse obstetric populations.
The questions are easy to both remember and score and can be asked by an obstetrician
or nurse in 1 minute. Women waiting for their prenatal appointments, for example,
could be asked to complete the T-ACE as part of a routine patient questionnaire
to be reviewed during the visit.

The TWEAK

The TWEAK is a
five-item screening tool that includes questions from the MAST, CAGE, and
T-ACE (see TWEAK textbox). The TWEAK is designed to detect alcoholism or heavy
drinking and was first tested in three male and female samples randomly selected
from three groups: (1) alcoholics in treatment at a county medical center;
(2) patients at two primary health care centers; and (3) the general population
of the Buffalo, New York, metropolitan area (Chan et al. 1993) . Subsequent
evaluation of the TWEAK has revealed its promise as a screening tool for identifying
pregnant women who are at-risk drinkers, defined as those consuming 1 ounce
of alcohol or more daily (Russell et al. 1994) .

TWEAK
T Tolerance: How many drinks can you hold?

W Have close friends
or relatives Worried or complained about your drinking in the past year?

E Eye Opener:
Do you sometimes take a drink in
the morning when you get up?

A Amnesia: Has
a friend or family member ever told
you about things you said or did while you were
drinking that you could not remember?

K( C) Do
you sometimes feel the need to Cut down on your drinking?

The TWEAK is used to screen for pregnancy risk drinking, defined here
as the consumption of 1 ounce or more of alcohol per day while pregnant.
Scores are calculated as follows: A positive response to question T
on Tolerance ( i. e. , consumption of more than five drinks) or question
W on Worry yields 2 points each; an affirmative reply to question E,
A, or K scores 1 point each. A total score of 2 or more points on the
TWEAK indicates a positive outcome for pregnancy risk drinking.

SOURCE: Chan et
al. 1993.

The TWEAK is scored on
a 7-point scale. On the tolerance question, 2 points are given if a woman
reports that she can consume more than five drinks without falling asleep
or passing out. A positive response to the worry question yields 2 points,
and positive responses to the last three questions yield 1 point each. A woman
who has a total score of 2 or more points is likely to be an at-risk drinker.

Like the T-ACE, the TWEAK asks about tolerance to the effects of alcohol.
In one study of 4,743 African-American women of low socioeconomic status who
were given the MAST, the CAGE, and the T-ACE tolerance question, the calculated
sensitivity and specificity of the TWEAK were 79 percent and 83 percent, respectively,
in contrast to the calculated 70-percent sensitivity and 85-percent specificity
of the T-ACE. Periconceptional risk drinking, defined as 1 ounce or more of
alcohol consumption per day or 14 drinks per week during a typical week before
pregnancy ( Russell et al. 1994) , was the criterion standard ( i. e. , this
was the level of drinking that the instruments were trying to detect) . The
ability to generalize these findings is limited. This is attributable to the
homogenous makeup of the sample, the fact that neither the T-ACE nor the TWEAK
were administered as independent instruments, and the definition of periconceptional
risk drinking, which other researchers have subsequently updated to 0.5 ounces
of alcohol per day (Hankin and Sokol 1995) .

The TWEAK does not appear to offer any significant advantages over the T-ACE.
Most studies investigating the TWEAK s performance have relied on a
definition of risk drinking that does not reflect more current research. Nonetheless,
it offers another option for clinicians.

Other Screening Questionnaires

Research has not established
the utility of other screening questionnaires - the CAGE, SMAST, AUDIT, and
Prenatal Alcohol Use Interview - for pregnant women. The CAGE and the SMAST
are popular self-report measures of alcoholism and are well studied in alcoholic
and nonalcoholic subjects and among males ( Bradley et al. 1998) . The AUDIT
is a 10-item questionnaire that identifies harmful and hazardous drinking
during the past year and has been validated in six countries (Cherpitel 1995).
The Prenatal Alcohol Use Interview is a 13-item questionnaire that has been
tested in a sample of 56 women thus far and requires further evaluation (Budd
et al. 2000) .

Two large studies of disadvantaged, minority, obstetric patients (Hankin and
Sokol 1995; Russell et al. 1996) reported that the calculated sensitivity
and specificity of the T-ACE and TWEAK were superior to the CAGE in identifying
risk drinking (defined as 1 ounce or more of alcohol consumption per day)
.In another study, we gave the SMAST, AUDIT, and T-ACE questions independently
to 350 pregnant women ( Chang et al. 1998) and calculated how well each of
the three instruments could predict lifetime DSM-III-R alcohol diagnoses and
any drinking during pregnancy. The SMAST did not perform better than chance
as a predictor for either of the two drinking categories. Although the AUDIT
had good predictive ability, the definition of a positive score on the AUDIT
for drinking pregnant women remains to be identified and confirmed through
further research.

Laboratory Tests for
Detecting Alcohol Use

Although the central focus
of this article is on screening questionnaires, other methods of detecting
alcohol use during pregnancy deserve some comment. Use of breath analysis
or urinalysis in pregnant patients is not likely to be feasible or acceptable,
given the rapid metabolism of alcohol and the pattern of drinking by most
pregnant women ( i. e. , it is unlikely that pregnant women will consume alcohol
right before their obstetric appointment) (Testa and Reifman 1996; Lundberg
et al. 1997; Strano-Rossi 1999) . However, recent research has demonstrated
the potential value of maternal blood markers for detecting levels of alcohol
use during pregnancy that may result in overt alcohol-related deficits in
newborns. However, the most significant and most common result of prenatal
alcohol expo-sure, neurobehavioral dysfunction, is not an outcome recognized
in the new-born period. Therefore, research has yet to establish the relevance
of these blood markers to the more common fetal alcohol effects ( Jones and
Chambers 1998; Stoller et al. 1998) . (See the article by Bearer on pp. xx-xx
of this issue for more information on potential biomarkers to detect alcohol
use during pregnancy.)

Summary

Simple screening questionnaires,
such as the T-ACE, provide valuable tools for identifying women who are using
alcohol during pregnancy. The T-ACE has been shown to identify any alcohol
consumption during pregnancy as well as higher amounts of drinking. Research
has demonstrated that any alcohol con ­ sumption during pregnancy increases
the risk of continued drinking during pregnancy ( Chang et al. 1999) .

The T-ACE is administered easily. A clinician may either ask the T-ACE questions
directly or request that the patient complete the questionnaire while waiting
for her appointment. The T ­ ACE has been tested and demonstrated to be acceptable
and effective in both formats.

A positive screen is not an indictment. Rather, it is an opportunity for the
clinician and patient to discuss prenatal alcohol exposure. The discussion
may lead the clinician to refer the patient for a diagnostic assessment. Or
the clinician may offer a brief intervention if the patient does not have
a severe alcohol problem. Because most pregnant women are highly motivated
to change their behaviors (Hankin et al. 2000) , brief interventions ( i.
e. , short counseling sessions) may be especially effective in this population.
Given the potential adverse consequences of prenatal alcohol exposure, short
screening questionnaires are worthwhile preventive measures.